2023 Volume 48 Issue 4 Pages 349-355
Since insurance coverage for the “cancer gene panel test” began in June 2019 in Japan, there has been significant anticipation for cancer genome medicine in pediatric brain tumors. The BRAF p.V600E mutation in gliomas is a notable actionable gene mutation that is effectively targeted by molecular targeted drugs. This is evidenced by numerous clinical trials showing promising results with such therapies. We experienced three pediatric malignant brain tumor cases in which the BRAF p.V600E mutation was detected using the cancer gene panel test (Foundation One®), and discuss the current status of these tests for pediatric brain tumors.
Case 1 involved an 18-year-old female with a left temporal lobe tumor that was discovered during an investigation of epileptic seizures. Following tumor resection, she was diagnosed with epithelioid glioblastoma. Despite the standard therapy, the tumor progressed rapidly. She was considered for molecular targeted therapy targeting the BRAF p.V600E mutation under a patient-directed care program. However, due to her deteriorating condition, she could not participate in the trial and died on day 215.
In Case 2, a 13-year-old female exhibited intratumoral hemorrhage in the interhemispheric fissure, which was found during a headache investigation. Eleven days after intracranial tumor resection, she experienced sudden intraspinal hemorrhage with paraplegia due to spinal dissemination. Diagnosed with epithelioid glioblastoma in both lesions, she was also considered for the same molecular targeted therapy as in Case 1. Unfortunately, similar to Case 1, her condition worsened, preventing trial participation, and leading to death on day 154.
Case 3 describes an 11-year-old female with recurrent absence seizures. A neoplastic lesion in the right temporal lobe was diagnosed as ganglioglioma with anaplastic features. Given the partial anaplasia in the pathological findings, postoperative treatment was necessary. However, concerns about potential adverse effects of radiation therapy, such as secondary malignancies, were prominent. Therefore, she was enrolled in the Patient’s Advised Treatment Program and started receiving molecular targeted therapy for the BRAF p.V600E mutation.
All three patients underwent cancer gene panel testing up to the expert panel level. However, only one patient received the molecular targeted therapy. The low rate of access to these drugs is a significant issue in cancer genomic medicine. For rapidly progressing malignancies, as seen in Cases 1 and 2, expedited cancer panel testing and institutional improvement are crucial. In addition, easing the conditions for clinical trial participation is essential. Conversely, there is often hesitation in treating malignant pediatric brain tumors with chemotherapy or radiation due to potential late complications that can impact development and quality of life. Case 3 demonstrates that molecular targeted agents might offer a new treatment avenue for pediatric malignant brain tumors, potentially reducing late complications while maintaining treatment efficacy.
